title: Antagonistic and synergistic effects of bone morphogenetic protein 2/7 and all-trans retinoic acid on the osteogenic differentiation of rat bone marrow stromal cells.
abstract: The osteogenesis of bone marrow stromal cells (BMSCs) is of paramount importance for the repair of large-size bone defects, which may be compromised by the dietary-accumulated all-trans retinoic acid (ATRA). We have shown that heterodimeric bone morphogenetic protein 2/7 (BMP2/7) could induce bone regeneration in a significantly higher dose-efficiency in comparison with homodimeric BMPs. In this study, we evaluated the effects of ATRA and BMP2/7 on the proliferation, differentiation, mineralization and osteogenic genes. ATRA and BMP2/7 exhibited both antagonistic and synergistic effects on the osteogenesis of BMSCs. ATRA significantly inhibited proliferation and expression of osteocalcin but enhanced the activity of alkaline phosphatase of BMSCs. On day 21, 50 ng/mL BMP2/7 could antagonize the inhibitive effects of ATRA and significantly enhance osteogenesis of BMSCs. These findings suggested a promising application potential of heterodimeric BMP2/7 in clinic to promote bone regeneration for the cases with dietary accumulated ATRA.
authors.affiliation: School/Hospital of Stomatology, Zhejiang University, Yan'an St. 395, Hangzhou, Zhejiang, 310006, China.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Bi
authors.affiliation: School/Hospital of Stomatology, Zhejiang University, Yan'an St. 395, Hangzhou, Zhejiang, 310006, China.|School of Stomatology, Hangzhou Dental Hospital, Zhejiang Chinese Medical University, 97 Mailbox, Binwen Road 548, Binjiang District, Hangzhou, 310053, China.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Gu
authors.affiliation: School of Stomatology, Hangzhou Dental Hospital, Zhejiang Chinese Medical University, 97 Mailbox, Binwen Road 548, Binjiang District, Hangzhou, 310053, China.
authors.forename: Yuanna
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Stomatology, No. 117th Hospital of People's Liberation Army, Airport Road 40, Hangzhou, Zhejiang, 310004, China.
authors.forename: Limin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU-University of Amsterdam, Research Institute MOVE, VU University, Gustav Mahlerlaan 3004, Amsterdam, 1018LA, the Netherlands.
authors.forename: Jing
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Oral Implantology and Prosthetic Dentistry, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU-University of Amsterdam, Research Institute MOVE, VU University, Gustav Mahlerlaan 3004, Amsterdam, 1018LA, the Netherlands.
authors.forename: Gang
authors.initials: G
authors.lastname: Wu
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000880:Anthraquinones; D001854:Bone Marrow Cells / Q000166:cytology*; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism* / Q000494:pharmacology; D055419:Bone Morphogenetic Protein 7 / Q000378:metabolism* / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D017931:DNA Primers / Q000235:genetics; D019281:Dimerization; D005434:Flow Cytometry; D005453:Fluorescence; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics*; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D017154:Stromal Cells / Q000502:physiology*; D014212:Tretinoin / Q000378:metabolism*
chemical_list: D000880:Anthraquinones; C525720:Bmp2 protein, rat; C525821:Bmp7 protein, rat; D055396:Bone Morphogenetic Protein 2; D055419:Bone Morphogenetic Protein 7; D017931:DNA Primers; D014212:Tretinoin; C010078:alizarin
keywords: all-trans retinoic acid; bone marrow stromal cells; bone morphogenetic protein; heterodimeric; osteogenic differentiation